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The inhibition of acetylcholinesterase (AChE) by cholinergic agents has been promoted as a potent strategy for treating and managing cognitive decline disorders. A wide range of natural products has long been used as potential sources or formulations of cholinergic inhibitors. Therefore, this study aimed to evaluate different Rosmarinus officinalis L. (R. officinalis) extracts for their AChE inhibitory activity using galanthamine as a standard AChE inhibitor. In this study, the ethyl-acetate extract (at a concentration of 250 µg/mL) exhibited the greatest inhibitory effect against AChE with significant inhibition of 75%, comparable to the inhibitor galanthamine with an inhibition of 88%. Kinetic analysis revealed that the extracts could induce a mixed type of inhibition, as observed in the case of galanthamine, with the highest increased Km and decreased Vmax values in the ethyl acetate extract. The antioxidant potential of the three extracts tested was found to be in the order of ethyl-acetate &gt; ethanol &gt; aqueous, with IC50 values of 272 µg/mL, 387 µg/mL, and 534 µg/mL, respectively. Ethyl-acetate was found to have the highest total phenolic content in all extracts. Further, in silico study showed structural binding characterization of rosmarinic acid and carnosic acid with human AChE enzyme. Rosmarinic acid showed strong binding and formed two hydrogen-bonding interactions with Ser-293 and Arg-296. In light of this, the ethyl-acetate extract of the plant may provide some novel potential pharmacological leads for treating and managing cognitive disorders such as Alzheimer’s.

Phytochemical Screening of Rosmarinus officinalis L. as a Potential Anticholinesterase and Antioxidant–Medicinal Plant for Cognitive Decline Disorders